Scientists keep finding new and unexpected benefits to vaccines
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“My colleagues who were looking through the databases said,
‘Hey, we found a signal that the influenza vaccine seems to be associated with
less Alzheimer’s. Is that something you know already?’” Schultz told CIDRAP
News. “I was like, ‘Oh my God; that’s totally unexpected.’”
The team began researching the relationship between
receiving a flu vaccine and Alzheimer’s disease risk. Their first paper compared people who
received the regular flu vaccine with those who didn’t and estimated the
likelihood of each group to develop Alzheimer’s.
“Three years of receiving the influenza vaccine was
associated with a 20% reduced risk, and six years was associated with a 40%
reduced risk of Alzheimer’s for at least eight years,” Schultz explained. “It’s
an association, not a cause and effect, but quite striking.”
Over the past several years, more research has emerged
showing a relationship between some adult vaccines and a lower risk of
dementia. Recent studies show an association between receiving the recombinant
shingles and flu vaccines and a lower risk of Alzheimer’s disease and other
types of dementia.
“The vaccines themselves are different. But why are they
starting to show some signals that they might be reducing risk of dementia or
Alzheimer’s disease?” asked Glen Finney, MD, director of the Memory and
Cognition Program at Geisinger Health and a fellow of the American Academy of
Neurology. “Well, what are vaccines doing? They’re re-training your immune
system.”
High- vs standard-dose flu vaccine performance
In their first paper, Schultz and his colleagues compared
people 65 years or older who received a flu vaccine to those who did not. “It
was actually protective,” he said. “We spent a lot of time trying to verify
that to the extent that we could.”
But then another question arose. Would the high-dose flu
vaccines that many adults 65 and older receive also offer the same benefit? In
this study, the researchers compared people who received a standard-dose flu
vaccine to those who received a high-dose flu vaccine. That helped them control
for what’s known as at the healthy vaccinee bias: People who regularly receive
vaccines tend to be healthier overall than those who do not.
“The high dose did
better than the standard dose by like 15%. So it wasn’t a huge amount, but it
was measurable,” Schultz explained. “It turns out that the anti-dementia
effects last a couple of years. In the paper, we showed that that it’s about
two years plus that the anti-dementia effects last—even though the anti-flu
effect only lasts four to six months.”
Women, who develop Alzheimer’s disease twice as often as
men, experienced a greater benefit from vaccination than men, too. “In women,
the high dose was much more effective than the standard dose,” he said. “That’s
a really interesting finding.”
The papers describe an association—not a causal relationship. Schultz and his colleagues are using mouse models to try to understand the mechanisms behind why a high-dose flu vaccine contributes to a lower risk of Alzheimer’s disease.
It’s possible that the vaccine trains the immune system to
reduce the amount of amyloid plaque, or tangled proteins that contribute to
Alzheimer’s, in the brain. Another theory is that the flu vaccine calms the
immune system so it doesn’t activate the amyloid plaques.
“You’d still deposit amyloid, but if you didn’t react to it,
maybe you don’t get the disease,” Schultz said.
Shingles virus, stroke, and dementia
After the live-attenuated shingles vaccine was approved in
the early 2000s, research emerged that showed a link between the vaccine and a
lower risk of dementia. Since then, the recombinant shingles vaccine has
replaced the live-attenuated vaccine.
Daniel Harris, PhD, of the University of Delaware, and
colleagues wondered if the recombinant vaccine would show the same association.
They examined nursing home electronic health record data and Medicare claims to
determine if receiving at least one dose of the shingles vaccine reduced the
risk of dementia over the next four years. In June, they published their paper in
the Annals of Internal Medicine.
“We found that there was about a 24% lower relative risk of
dementia in people who got the vaccine,” Harris said. “We required people to
get at least one dose, because it’s a two-dose series. That said, most people
in that exposure group ended up getting two doses.”
Again, the reason the shingles vaccine seemingly protects
people from dementia remains unclear. But experts know that the varicella
zoster virus, which causes chickenpox and, if reactivated, shingles, thrives in
the nerves.
“It lives in the dorsal ganglion in your spine, and it can
also live in your cranial nerves, and it can actually cause neuroinflammation
without actually showing a classic shingles rash later on in life,” Harris
said. “The varicella zoster virus is also one of the only, if not only, human
viruses that is known to replicate in cerebral arteries.”
This causes inflammation in the arteries in the brain, where
it changes the cerebrovascular architecture. In theory, those changes could
contribute to dementia. What’s more, the risk of stroke increases for up to a
year after shingles onset. “Stroke is a major risk factor for dementia,” Harris
said. “It’s called vascular dementia.”
TB vaccine’s ‘very surprising and curious result’
While the Bacille Calmette-Guerin (BCG) vaccine prevents
tuberculosis (TB), it’s not commonly used in the United States except for rare
indications such as the treatment of some bladder cancers. Scientists at Mass
General Brigham studying its off-label uses noticed that BCG seemed to provide
an unexpected benefit.
“Some of the results started coming out saying, ‘Look, it
seems like the people who were getting BCG were having less incidence of
Alzheimer’s disease and all kinds of other dementia,’” Marc Weinberg, MD, PhD,
of Massachusetts General Hospital, said. “That was a very surprising and
curious result.”
Weinberg and his colleagues designed a small open-label
study to examine whether BCG immunotherapy can enter the central nervous
system. They looked at 23 adults aged 55 and older, of which 11 had Alzheimer’s
and 12 did not. They tested cerebral spinal fluid with a lumbar puncture to
show that BCG could reach the brain. The study was published in July
in Communications Medicine.
“What we didn’t do is prove that BCG prevents Alzheimer’s.
We didn’t prove that it treats it,” Weinberg said. “What we showed is that, in
older adults, including a population that also has a clear pathology of
Alzheimer’s, BCG is getting into the central nervous system and is changing the
way it’s working, in how the immune system is working.”
Are vaccines a key to healthy aging?
Americans are increasingly looking for ways to bolster their health and live longer. Could keeping up with adult vaccinations be a way to do that?
Experts agree that the data show only associations, so more
research—including randomized clinical trials comparing the vaccines to a
placebo—is needed.
“We need to understand the underlying mechanisms there,”
Harris said. “We know randomized trials are really good when they’re well
designed at reducing the influence of many biases. That would be another really
important piece of the puzzle.”
Such research would be time consuming, because a vaccine’s
impact on preventing dementia wouldn’t be immediately apparent. After age 50,
when people can receive a recombinant shingles vaccine, cognitive changes may
take many years to become apparent.
“These trials are going to need a lot of time,” Harris
explained. “That introduces a lot of methodological complexity about follow-up
and how long you can follow people forward and ascertain outcomes.”
Finney also wonders if other vaccines could also be
associated with lower dementia risk. “We need to look at just how wide-ranging
this effect is. Is it generic to any vaccine that modulates the immune system,
or is it a subset of vaccines?” Finney asked. “From the studies we’re
seeing, it looks like it might be a pretty wide effect. But we need to verify
that.”
Still, if vaccines are shown to provide the unexpected
effect of less dementia, it would be another incentive for older adults to keep
current with their vaccines.
“The flu vaccine can keep patients out of the hospital, can
keep them out of the ICU [intensive care unit], and can keep them out of the
morgue,” said Finney. “So that to me is, in and of itself, a good enough
reason. But then add to that it might help you to protect your brain health and
reduce your risk of dementia; that to me is a win.”
